Objectives To understand the role of OspA in the immunobiology of Borrelia burgdorferi. Results A Lyme disease vaccine, based on the Borrelia burgdorferi lipoprotein OspA, has recently undergone phase III trials in humans. The results of one of these trials indicate that vaccine efficacy positively correlates with anti-OspA antibody titer. Spirochete killing within the tick vector midgut, upon which vaccine efficacy appears to depend, could occur chiefly via a mechanism that involves antibody alone, as it has been reported that complement is degraded by tick-saliva decomplementing factors. We compared the in vitro killing efficiency of anti-OspA antibody elicited in rhesus monkeys by the OspA vaccine, in the presence and in the absence of monkey complement. Killing in the absence of complement was between 14 and 3,800 times less efficient than with complement present, depending on spirochete strain. The relative inefficiency of the complement independent killing mechanism by anti-Osp A antibody may explain why the OspA vaccine efficacy is critically dependent on antibody titer. Future directions to further explore the role of OspA in tick transmission by investigating efficiency of transmission of B. burgdorferi mutants that express truncated forms of OspA. FUNDING Grant U50/CCU606604 from the Centers for Disease Control and Prevention, AI35027 from the NIAID, and the Base grant. PUBLICATIONS Nowling, J., and Philipp, M. T. 1999. Killing of Borrelia burgdorferi by antibody to the OspA vaccine is inefficient in the absence of complement. Infect. Immun. 67, 443-445. Soli, M., Bantar, C., Indest, K., Gu, Y., Ramamoorthy, R. Coughlin, R. and Philipp, M. T. 1998. Borrelia burgdorferi escape mutants that survive in the presence of antiserum to the OspA vaccine are killed when complement is also present. Infect. Immun. 66, 2540-2546. Philipp, M. T. Studies on OspA, a source of new paradigms in Lyme disease Research. 1998. Trends Microbiol., 6, 44-47.